6aaf | pdb_00006aaf
Crystal structure of fission yeast Atg8 complexed with the helical AIM of Hfl1.
Structural highlights
FunctionATG8_SCHPO Ubiquitin-like modifier involved in autophagosomes formation. With atg4, mediates the delivery of the autophagosomes to the vacuole via the microtubule cytoskeleton. Required for selective autophagic degradation of the nucleus (nucleophagy) as well as for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Participates also in membrane fusion events that take place in the early secretory pathway. Also involved in endoplasmic reticulum-specific autophagic process and is essential for the survival of cells subjected to severe ER stress. The atg8-PE conjugate mediates tethering between adjacent membranes and stimulates membrane hemifusion, leading to expansion of the autophagosomal membrane during autophagy (By similarity). Contributes to the maintenance of cell viability under conditions of nitrogen-depletion. Plays a role in meiosis and sporulation and contributes to oxidative stress resistance (PubMed:17295836, PubMed:19778961, PubMed:20070859).[UniProtKB:P38182][1] [2] [3] Publication Abstract from PubMedThe ubiquitin-like protein Atg8, in its lipidated form, plays central roles in autophagy. Yet, remarkably, Atg8 also carries out lipidation-independent functions in non-autophagic processes. How Atg8 performs its moonlighting roles is unclear. Here we report that in the fission yeast Schizosaccharomyces pombe and the budding yeast Saccharomyces cerevisiae, the lipidation-independent roles of Atg8 in maintaining normal morphology and functions of the vacuole require its interaction with a vacuole membrane protein Hfl1 (homolog of human TMEM184 proteins). Crystal structures revealed that the Atg8-Hfl1 interaction is not mediated by the typical Atg8-family-interacting motif (AIM) that forms an intermolecular beta-sheet with Atg8. Instead, the Atg8-binding regions in Hfl1 proteins adopt a helical conformation, thus representing a new type of AIMs (termed helical AIMs here). These results deepen our understanding of both the functional versatility of Atg8 and the mechanistic diversity of Atg8 binding. Lipidation-independent vacuolar functions of Atg8 rely on its noncanonical interaction with a vacuole membrane protein.,Liu XM, Yamasaki A, Du XM, Coffman VC, Ohsumi Y, Nakatogawa H, Wu JQ, Noda NN, Du LL Elife. 2018 Nov 19;7. pii: 41237. doi: 10.7554/eLife.41237. PMID:30451685[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
| ||||||||||||||||||
